Medical Genetics: Types of Genetic Changes - Health Encyclopedia - University of Rochester Medical Center URMC / Encyclopedia / Content Medical Genetics: Types of Genetic Changes The human body has 20,000 to 25,000 different genes. Genes are located on chromosomes, which are stick-shaped structures in the middle of each cell in the body. Each cell usually has 46 chromosomes grouped in 23 pairs. Each gene has a specific function. And when a gene or chromosome is abnormal, it may cause health problems in the body. There are 2 main types of genetic changes: Chromosome abnormalities Single-gene defects What are chromosome abnormalities? Chromosome abnormalities in the baby may be inherited from the parent or may occur with no family history. These are the most common: Aneuploidy This means more or fewer chromosomes than the normal number. Examples include: Down syndrome (trisomy 21). Cells contain 3 copies of the 21st chromosome. Turner syndrome. One of the two sex chromosomes is not transferred. This leaves a single X chromosome for 45 total chromosomes instead of 46. Deletion This is when part of a chromosome is missing, or part of the DNA code is missing.

Inversion This is when a chromosome breaks and the piece of it turns around and reattaches itself. Inversions can be passed down in families, but they may or may not cause birth defects. Ring A ring chromosome is one where the ends are attached to itself to form a ring. Rings can be passed down in families. They may or may not cause health problems. Translocation This is when a chromosome segment rearranges from one location to another. It can happen either within the same chromosome or move to another chromosome. There are two types: Balanced translocation. This is when the DNA is equally exchanged between chromosomes. No DNA is lost or added. A parent with a balanced translocation is healthy, but he or she may be at risk for passing on unbalanced chromosomes to a child. Robertsonian translocation. This is a balanced translocation in which one chromosome joins the end of another. Mosaicism This is when a person has 2 or more sets of chromosomes in his or her cells with different genetic material. What are single-gene changes? A change in a single gene causes a defect or abnormality. Single-gene changes usually have a higher risk of being passed on to children.

Single-gene changes can be: Dominant This means the abnormality occurs when only one of the genes from one parent is abnormal. If the parent has the disorder, the baby has a 1 in 2 chance of inheriting it. Examples include: Achondroplasia. This is a bone development disorder that causes dwarfism. Marfan syndrome. This is a connective tissue disorder that causes long limbs and heart defects. Recessive This means the abnormality only occurs when both parents have abnormal genes. If both parents are carriers, a baby has a 1 in 4 chance of having the disorder. Examples include: Cystic fibrosis. This is a disorder of glands that causes excess mucus in the lungs. It also causes problems with how the pancreas works and with how food is absorbed. Sickle cell disease. This condition causes abnormal red blood cells that don’t carry oxygen normally. Tay-Sachs disease. This is an inherited autosomal recessive condition that causes the central nervous system to decline. The condition is fatal, usually by age 5. X-linked The disorder is determined by genes on the X chromosome. Males are mainly affected and have the disorder.

Daughters of men with the disorder are carriers of the trait and have a 1 in 2 chance of passing it to their children. Sons of women who are carriers each have a 1 in 2 chance of having the disorder. Examples include: Duchenne muscular dystrophy. This is a disease that causes muscle wasting. Hemophilia. This is a bleeding disorder caused by low levels or lack of a blood protein that is needed for clotting. How genetic changes are passed along in a family The way a gene is inherited can help determine the risk of it in a current or future pregnancy. The risk of having a baby with a birth defect from a genetic change increases if: The parents have another child with a genetic disorder. There is a family history of a genetic disorder. One parent has a chromosome abnormality. The baby in the womb has abnormalities seen on an ultrasound. Families at risk for genetic diseases may want to talk with a certified genetic counselor. Making a chart of members of the family and their health histories can help show risks for certain problems. Genetic counseling also helps parents understand the effects of a disorder and ways it may be prevented or treated. Getting genetic testing Each parent's DNA may need to be checked.

This is done to learn about some genetic inheritance patterns. Prenatal testing can also be done to check the baby in the womb for problems. Testing may include: Ultrasound. This test uses sound waves to look at how a baby in the womb is growing. Chorionic villus sampling (CVS). This test uses a sample of tissues around the baby to look for problems. Amniocentesis. This test uses a sample of the amniotic fluid from the sac around the baby to check for problems. Medical Reviewers: hemophilia - Genetics Home Reference hemophilia Description Hemophilia is a bleeding disorder that slows the blood clotting process . People with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, continuous bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia do not necessarily involve spontaneous bleeding, and the condition may not become apparent until abnormal bleeding occurs following surgery or a serious injury.

The major types of this condition are hemophilia A (also known as classic hemophilia or factor VIII deficiency) and hemophilia B (also known as Christmas disease or factor IX deficiency). Although the two types have very similar signs and symptoms, they are caused by mutations in different genes. People with an unusual form of hemophilia B, known as hemophilia B Leyden, experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty. Frequency The two major forms of hemophilia occur much more commonly in males than in females. Hemophilia A is the most common type of the condition; 1 in 4,000 to 1 in 5,000 males worldwide are born with this disorder. Hemophilia B occurs in approximately 1 in 20,000 newborn males worldwide. Related Information Genetic Changes Changes in the F8 gene are responsible for hemophilia A, while mutations in the F9 gene cause hemophilia B. The F8 gene provides instructions for making a protein called coagulation factor VIII. A related protein, coagulation factor IX, is produced from the F9 gene. Coagulation factors are proteins that work together in the blood clotting process .

After an injury, blood clots protect the body by sealing off damaged blood vessels and preventing excessive blood loss. Mutations in the F8 or F9 gene lead to the production of an abnormal version of coagulation factor VIII or coagulation factor IX, or reduce the amount of one of these proteins. The altered or missing protein cannot participate effectively in the blood clotting process . As a result, blood clots cannot form properly in response to injury. These problems with blood clotting lead to continuous bleeding that can be difficult to control. The mutations that cause severe hemophilia almost completely eliminate the activity of coagulation factor VIII or coagulation factor IX. The mutations responsible for mild and moderate hemophilia reduce but do not eliminate the activity of one of these proteins. Another form of the disorder, known as acquired hemophilia, is not caused by inherited gene mutations. This rare condition is characterized by abnormal bleeding into the skin, muscles, or other soft tissues, usually beginning in adulthood. Acquired hemophilia results when the body makes specialized proteins called autoantibodies that attack and disable coagulation factor VIII. The production of autoantibodies is sometimes associated with pregnancy, immune system disorders, cancer, or allergic reactions to certain drugs.

In about half of cases, the cause of acquired hemophilia is unknown. Inheritance Pattern Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern . The genes associated with these conditions are located on the X chromosome , which is one of the two sex chromosomes . In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, it is very rare for females to have hemophilia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. Carrier females have about half the usual amount of coagulation factor VIII or coagulation factor IX, which is generally enough for normal blood clotting. However, about 10 percent of carrier females have less than half the normal amount of one of these coagulation factors; these individuals are at risk for abnormal bleeding, particularly after an injury, surgery, or tooth extraction.

Related Information Coagulation Disorders | definition of Coagulation Disorders by Medical dictionary Coagulation Disorders | definition of Coagulation Disorders by Medical dictionary Definition Coagulation disorders deal with disruption of the body's ability to control blood clotting. The most commonly known coagulation disorder is hemophilia , a condition in which patients bleed for long periods of time before clotting. There are other coagulation disorders with a variety of causes. Description Coagulation, or clotting, occurs as a complex process involving several components of the blood. Plasma, the fluid component of the blood, carries a number of proteins and coagulation factors that regulate bleeding. Platelets, small colorless fragments in the blood, initiate contraction of damaged blood vessels so that less blood is lost. They also help plug damaged blood vessels and work with plasma to accelerate blood clotting. A disorder affecting platelet production or one of the many steps in the entire process can disrupt clotting. Coagulation disorders arise from different causes and produce different complications. Some common coagulation disorders are: Hemophilia, or hemophilia A (Factor VIII deficiency), an inherited coagulation disorder, affects about 20,000 Americans.

This genetic disorder is carried by females but most often affects males. Christmas disease, also known as hemophilia B or Factor IX deficiency, is less common than hemophilia A with similar in symptoms. Disseminated intravascular coagulation disorder, also known as consumption coagulopathy, occurs as a result of other diseases and conditions. This disease accelerates clotting, which can actually cause hemorrhage. Thrombocytopenia is the most common cause of coagulation disorder. It is characterized by a lack of circulating platelets in the blood. This disease also includes idiopathic thrombocytopenia. Von Willebrand's disease is a hereditary disorder with prolonged bleeding time due to a clotting factor deficiency and impaired platelet function. It is the most common hereditary coagulation disorder. Hypoprothrombinemia is a congenital deficiency of clotting factors that can lead to hemorrhage. Other coagulation disorders include Factor XI deficiency, also known as hemophilia C, and Factor VII deficiency. Hemophilia C afflicts one in 100,000 people and is the second most common bleeding disorder among women.

Factor VII is also called serum prothrombin conversion accelerator (SPCA) deficiency. One in 500,000 people may be afflicted with this disorder that is often diagnosed in newborns because of bleeding into the brain as a result of traumatic delivery. Causes and symptoms Some coagulation disorders present symptoms such as severe bruising. Others will show no apparent symptoms, but carry the threat of severe internal bleeding. Hemophilia Because of its hereditary nature, hemophilia A may be suspected before symptoms occur. Some signs of hemophilia A are numerous large, deep bruises and pain and swelling of joints caused by internal bleeding. Patients with hemophilia do not bleed faster, just longer. A person with mild hemophilia may first discover the disorder with prolonged bleeding following a surgical procedure. If there is bleeding into the neck, head, or digestive tract, or bleeding from an injury, emergency measures may be required. Mild and severe hemophilia A are inherited through a complex genetic system that passes a recessive gene on the female chromosome. Women usually do not show signs of hemophilia but are carriers of the disease.

Each male child of the carrier has a 50% chance of having hemophilia, and each female child has a 50% chance of passing the gene on. Christmas disease Christmas disease, or hemophilia B, is also hereditary but less common than hemophilia A. The severity of Christmas disease varies from mild to severe, although mild cases are more common. The severity depends on the degree of deficiency of the Factor IX (clotting factor). Hemophilia B symptoms are similar to those of hemophilia A, including numerous, large and deep bruises and prolonged bleeding. The more dangerous symptoms are those that represent possible internal bleeding, such as swelling of joints, or bleeding into internal organs upon trauma. Hemophilia most often occurs in families with a known history of the disease, but occasionally, new cases will occur in families with no apparent history. Disseminated intravascular coagulation The name of this disorder arises from the fact that malfunction of clotting factors cause platelets to clot in small blood vessels throughout the body. This action leads to a lack of clotting factors and platelets at a site of injury that requires clotting.

Patients with disseminated intravascular coagulation (DIC) will bleed abnormally even though there is no history of coagulation abnormality. Symptoms may include minute spots of hemorrhage on the skin, and purple patches or hematomas caused by bleeding in the skin. A patient may bleed from surgery or intravenous injection (IV) sites. Related symptoms include vomiting, seizures, coma , shortness of breath, shock, severe pain in the back, muscles, abdomen, or chest. DIC is not a hereditary disorder or a common one. It is most commonly caused by complications during pregnancy or delivery, overwhelming infections, acute leukemia, metastatic cancer , extensive burns and trauma, and even snakebites. There are a number of other causes of DIC, and it is not commonly understood why or how these various disorders can lead to the coagulation problem. What the underlying causes of DIC have in common is some factor that affects proteins, platelets, or other clotting factors and processes. For example, uterine tissue can enter the mother's circulation during prolonged labor, introducing foreign proteins into the blood, or the venom of some exotic snakes can activate one of the clotting factors. Severe head trauma can expose blood to brain tissue.

No matter the cause of DIC, the results are a malfunction of thrombin (an enzyme) and prothrombin (a glycoprotein), which activate the fibrinolytic system, releasing clotting factors in the blood. DIC can alternate from hemorrhage to thrombosis, and both can exist, which further complicates diagnosis and treatment. Thrombocytopenia Thrombocytopenia may be acquired or congenital. It represents a defective or decreased production of platelets. Symptoms include sudden onset of small spots of hemorrhage on the skin, or bleeding into mucous membranes (such as nosebleeds). The disorder may also be evident as blood in vomit or stools, bleeding during surgery, or heavy menstrual flow in women. Some patients show none of these symptoms, but complain of fatigue and general weakness. There are several causes of thrombocytopenia, which is more commonly acquired as a result of another disorder. Common underlying disorders include leukemia, drug toxicity, or aplastic anemia , all of which lead to decreased or defective production of platelets in the bone marrow. Other diseases may destroy platelets outside the marrow.

These include severe infection, disseminated intravascular coagulation, and cirrhosis of the liver. The idiopathic form most commonly occurs in children, and is most likely the result of production of antibodies that cause destruction of platelets in the spleen and to a lesser extent the liver. Von Willebrand's disease is caused by a defect in the Von Willebrand clotting factor, often accompanied by a deficiency of Factor VIII as well. It is a hereditary disorder that affects both males and females. In rare cases, it may be acquired. Symptoms include easy bruising, bleeding in small cuts that stops and starts, abnormal bleeding after surgery, and abnormally heavy menstrual bleeding. Nosebleeds and blood in the stool with a black, tarlike appearance are also signs of Von Willebrand's disease. Hypoprothrombinemia This disorder is a deficiency in prothrombin, or Factor II, a glycoprotein formed and stored in the liver. Prothrombin, under the right conditions, is converted to thrombin, which activates fibrin and begins the process of coagulation. Some patients may show no symptoms, and others will suffer severe hemorrhaging.

Patients may experience easy bruising, profuse nosebleeds, postpartum hemorrhage, excessively prolonged or heavy menstrual bleeding, and postsurgical hemorrhage. Hypoprothrombinemia may also be acquired rather than inherited, and usually results from a Vitamin K deficiency caused by liver diseases, newborn hemorrhagic disease, or a number of other factors. Other coagulation disorders Factor XI deficiency, or hemophilia C, occurs more frequently among certain ethnic groups, with an incidence of about one in 10,000 among Ashkenazi Jews. Nearly 50% of patients with this disorder experience no symptoms, but others may notice blood in their urine, nosebleeds, or bruising. Although joint bleeding seldom occurs, some factor XI patients will experience bleeding long after an injury occurs. Some women will experience prolonged bleeding after childbirth . Patients with factor VII deficiency vary greatly in their bleeding severity. Women may experience heavy menstrual bleeding, bleeding from the gums or nose, bleeding deep within the skin, and episodes of bleeding into the stomach, intestine, and urinary tract. Factor VII patients may also suffer bleeding into joints. Diagnosis Several blood tests can be used to detect various coagulation disorders.

There are hundreds of different tests a doctor can order to look for indications of specific diseases. In addition to blood tests, physicians will complete a medical history and physical examination . In the case of acquired coagulation disorders, information such as prior or current diseases and medications will be important in determining the cause of the blood disorder. Hemohilia A will be diagnosed with laboratory tests detecting presence of clotting factor VIII, factor IX, and others, as well as the presence or absence of clotting factor inhibitors. Christmas disease will be checked against normal bleeding and clotting time, as well as for abnormal serum reagents in factor IX deficiency. Other tests of prothrombin time and thromboplastic generation may also be ordered. There is no one test or group of tests that can always make (or exclude) a diagnosis of DIC. DIC can be diagnosed through a number of laboratory tests which measure concentration of platelets and fibrinogen in the blood with normal counts and prolonged prothrombin time. Other supportive data include diminished levels of factors V, fibrinogen, and VIII, decreased hemoglobin, and others. Since many of the test results also indicate other disorders, the physician may have to put together several results to reach a diagnosis of DIC.

Serial tests may also be recommended, because a single examine at one moment in time may not reveal the process that is occurring. Tests for thrombocytopenia include coagulation tests revealing a decreased platelet count , prolonged bleeding time, and other measurements. If these tests indicate that platelet destruction is causing the disorder, the physician may order bone marrow examination. Von Willebrand's disease will be diagnosed with the assistance of laboratory tests which show prolonged bleeding time, absent or reduced levels of factor VIII, normal platelet count, and others. Hypothrombinemia is diagnosed with history information and the use of tests that measure vitamin K deficiency, deficiency of prothrombin, and clotting factors V, VII, IX, and X. Factor XI deficiency is diagnosed most often after injury-related bleeding. Blood tests can help pinpoint factor VII deficiency. Treatment In mild cases, treatment may involve the use of drugs that stimulate the release of deficient clotting factors. In severe cases, bleeding may only stop if the clotting factor that is missing is replaced through infusion of donated human blood in the form of fresh frozen plasma or cryoprecipitate.

Hemophilia A in mild episodes may require infusion of a drug called desmopressin or DDAVP. Severe bleeding episodes will require transfusions of human blood clotting factors. Hemophiliacs are encouraged to receive physical therapy to help damaged joints and to exercise in non-contact sports such as swimming, bicycle riding, or walking. Christmas disease patients are treated similarly to hemophilia A patients. There are commercial products and human blood products available to provide coagulation. Cryoprecipitate was invented in 1965 to replace the need for whole plasma transfusions, which introduced more volume than needed. By the 1970s, people were able to infuse themselves with freeze-dried clotting factor. Superficial wounds can be cleaned and bandaged. Parents of hemophiliac children receiving immunizations should inform the vaccination provider in advance to decrease the possibility of bleeding problems. These children should probably not receive injections which go into the muscle. Treatment for disseminated intravascular coagulation patients is complicated by the large variety of underlying causes of the disorder. If at all possible, the physician will first treat this underlying disorder. If the patient is not already bleeding, this supportive treatment may eliminate the DIC.

However, if bleeding is occurring, the patient may need blood, platelets, fresh frozen plasma, or other blood products. Heparin has been controversial in treating DIC, but it is often used as a last resort to stop hemorrhage. Heparin has not proven useful in treating patients with DIC resulting from heat stroke , exotic snakebites, trauma, mismatched transfusions, and acute problems resulting from obstetrical complications. Secondary acquired thrombocytopenia is best alleviated by treating the underlying cause or disorder. The specific treatment may depend on the underlying cause. Sometimes, corticosteroids or immune globulin may be given to improve platelet production. Von Willebrand's disease is treated by several methods to reduce bleeding time and to replace factor VIII, which consequently will replace the Von Willebrand factor. This may include infusion of cryoprecipitate or fresh frozen plasma. Desmopressin may also help raise levels of the Von Willebrand factor. Hypoprothrombinemia may be treated with concentrates of prothrombin. Vitamin K may also be produced, and in bleeding episodes, the patient may receive fresh plasma products.

Factor XI (hemophilia C) is most often treated with plasma, since there are no commercially available concentrates of factor XI in the United States. Factor VII patients may be treated with prothrombin complex concentrates. As of early 1998, factor VII concentrate was not licensed in the United States and could only be used with special permission. Alternative treatment This can be a very severe condition and should be managed by a practitioner of alternative medicine in conjunction with a medical doctor; this condition should not be self managed. For patients known to suffer from hemophilia A or B and other bleeding disorders, avoidance of activities that can cause severe injury should be practiced. Comprehensive care addresses the whole person by helping to deal with the psychosocial aspects of the disease. Prognosis The prognosis for patients with mild forms of coagulation disorders is normally good. Many people can lead a normal life and maintain a normal life expectancy. Without treatment of bleeding episodes, severe muscle and joint pain, and eventually, damage, can occur. Any incident that causes blood to collect in the head, neck, or digestive system can be very serious and requires immediate attention. DIC can be severe enough to cause clots to form and a stroke could occur.

DIC is also serious enough to cause gangrene in the fingers, nose or genitals. The prognosis depends on early intervention and treatment of the underlying condition. Hemorrhage from a coagulation disorder, particularly into the brain or digestive track, can prove fatal. In the past, patients who received regular transfusions of human blood products were subject to increased risk of AIDS and other diseases. However, efforts have been made since the early 1990s to ensure the safety of the blood supply. Prevention Prevention of coagulation disorders varies. Acquired disorders may only be prevented by preventing onset of the underlying disorder (such as cirrhosis). Hereditary disorders can be predicted with prenatal testing and genetic counseling . Prevention of severe bleeding episodes may be accomplished by refraining from activities that could cause injury, such as contact sports. Open communication with healthcare providers prior to procedures or tests that could cause bleeding may prevent a severe bleeding incident. Resources Creutzfeldt-Jakob Disease Fact Sheet | National Institute of Neurological Disorders and Stroke National Institute of Neurological Disorders and Stroke Where can I get more information? What is Creutzfeldt-Jakob disease?

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. It affects about one person in every one million people per year worldwide; in the United States there are about 300 cases per year. CJD usually appears in later life and runs a rapid course. Typically, onset of symptoms occurs about age 60, and about 90 percent of individuals die within 1 year. In the early stages of disease, people may have failing memory, behavioral changes, lack of coordination and visual disturbances. As the illness progresses, mental deterioration becomes pronounced and involuntary movements, blindness, weakness of extremities, and coma may occur. There are three major categories of CJD: In sporadic CJD, the disease appears even though the person has no known risk factors for the disease. This is by far the most common type of CJD and accounts for at least 85 percent of cases. In hereditary CJD, the person has a family history of the disease and/or tests positive for a genetic mutation associated with CJD. About 5 to 10 percent of cases of CJD in the United States are hereditary.

In acquired CJD, the disease is transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures. There is no evidence that CJD is contagious through casual contact with a CJD patient. Since CJD was first described in 1920, fewer than 1 percent of cases have been acquired CJD. CJD belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs). Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges under a microscope. CJD is the most common of the known human TSEs. Other human TSEs include kuru, fatal familial insomnia (FFI), and Gerstmann-Straussler-Scheinker disease (GSS). Kuru was identified in people of an isolated tribe in Papua New Guinea and has now almost disappeared. FFI and GSS are extremely rare hereditary diseases, found in just a few families around the world. Other TSEs are found in specific kinds of animals.

These include bovine spongiform encephalopathy (BSE), which is found in cows and is often referred to as “mad cow” disease; scrapie, which affects sheep and goats; mink encephalopathy; and feline encephalopathy. Similar diseases have occurred in elk, deer, and exotic zoo animals. What are the symptoms of the disease? CJD is characterized by rapidly progressive dementia. Initially, individuals experience problems with muscular coordination; personality changes, including impaired memory, judgment, and thinking; and impaired vision. People with the disease also may experience insomnia, depression, or unusual sensations. CJD does not cause a fever or other flu-like symptoms. As the illness progresses, mental impairment becomes severe. Individuals often develop involuntary muscle jerks called myoclonus, and they may go blind. They eventually lose the ability to move and speak and enter a coma. Pneumonia and other infections often occur in these individuals and can lead to death. There are several known variants of CJD. These variants differ somewhat in the symptoms and course of the disease.

For example, a variant form of the disease-called new variant or variant (nv-CJD, v-CJD), described in Great Britain and France-begins primarily with psychiatric symptoms, affects younger individuals than other types of CJD, and has a longer than usual duration from onset of symptoms to death. Another variant, called the panencephalopathic form, occurs primarily in Japan and has a relatively long course, with symptoms often progressing for several years. Scientists are trying to learn what causes these variations in the symptoms and course of the disease. Some symptoms of CJD can be similar to symptoms of other progressive neurological disorders, such as Alzheimer’s or Huntington’s disease. However, CJD causes unique changes in brain tissue which can be seen at autopsy. It also tends to cause more rapid deterioration of a person’s abilities than Alzheimer’s disease or most other types of dementia. How is CJD diagnosed? There is currently no single diagnostic test for CJD. When a doctor suspects CJD, the first concern is to rule out treatable forms of dementia such as encephalitis (inflammation of the brain) or chronic meningitis. A neurological examination will be performed and the doctor may seek consultation with other physicians.

Standard diagnostic tests will include a spinal tap to rule out more common causes of dementia and an electroencephalogram (EEG) to record the brain’s electrical pattern, which can be particularly valuable because it shows a specific type of abnormality in CJD. Computerized tomography of the brain can help rule out the possibility that the symptoms result from other problems such as stroke or a brain tumor. Magnetic resonance imaging (MRI) brain scans also can reveal characteristic patterns of brain degeneration that can help diagnose CJD. The only way to confirm a diagnosis of CJD is by brain biopsy or autopsy. In a brain biopsy, a neurosurgeon removes a small piece of tissue from the patient’s brain so that it can be examined by a neuropathologist. This procedure may be dangerous for the individual, and the operation does not always obtain tissue from the affected part of the brain. Because a correct diagnosis of CJD does not help the person, a brain biopsy is discouraged unless it is needed to rule out a treatable disorder. In an autopsy, the whole brain is examined after death. Both brain biopsy and autopsy pose a small, but definite, risk that the surgeon or others who handle the brain tissue may become accidentally infected by self-inoculation.

Special surgical and disinfection procedures can minimize this risk. A fact sheet with guidance on these procedures is available from the NINDS and the World Health Organization. Scientists are working to develop laboratory tests for CJD. One such test, developed at NINDS, is performed on a person’s cerebrospinal fluid and detects a protein marker that indicates neuronal degeneration. This can help diagnose CJD in people who already show the clinical symptoms of the disease. This test is much easier and safer than a brain biopsy. The false positive rate is about 5 to 10 percent. Scientists are working to develop this test for use in commercial laboratories. They are also working to develop other tests for this disorder. How is the disease treated? There is no treatment that can cure or control CJD. Researchers have tested many drugs, including amantadine, steroids, interferon, acyclovir, antiviral agents, and antibiotics. Studies of a variety of other drugs are now in progress. However, so far none of these treatments has shown any consistent benefit in humans. Current treatment for CJD is aimed at alleviating symptoms and making the individual as comfortable as possible.

Opiate drugs can help relieve pain if it occurs, and the drugs clonazepam and sodium valproate may help relieve myoclonus. During later stages of the disease, changing the person’s position frequently can keep him or her comfortable and helps prevent bedsores. A catheter can be used to drain urine if the individual cannot control bladder function, and intravenous fluids and artificial feeding also may be used. What causes Creutzfeldt-Jakob disease? Some researchers believe an unusual "slow virus" or another organism causes CJD. However, they have never been able to isolate a virus or other organism in people with the disease. Furthermore, the agent that causes CJD has several characteristics that are unusual for known organisms such as viruses and bacteria. It is difficult to kill, it does not appear to contain any genetic information in the form of nucleic acids (DNA or RNA), and it usually has a long incubation period before symptoms appear. In some cases, the incubation period may be as long as 50 years. The leading scientific theory at this time maintains that CJD and the other TSEs are caused by a type of protein called a prion.

Prion proteins occur in both a normal form, which is a harmless protein found in the body’s cells, and in an infectious form, which causes disease. The harmless and infectious forms of the prion protein have the same sequence of amino acids (the "building blocks" of proteins) but the infectious form of the protein takes a different folded shape than the normal protein. Sporadic CJD may develop because some of a person’s normal prions spontaneously change into the infectious form of the protein and then alter the prions in other cells in a chain reaction. Once they appear, abnormal prion proteins aggregate, or clump together. Investigators think these protein aggregates may lead to the neuron loss and other brain damage seen in CJD. However, they do not know exactly how this damage occurs. About 5 to 10 percent of all CJD cases are inherited. These cases arise from a mutation, or change, in the gene that controls formation of the normal prion protein. While prions themselves do not contain genetic information and do not require genes to reproduce themselves, infectious prions can arise if a mutation occurs in the gene for the body’s normal prion protein.

If the prion protein gene is altered in a person’s sperm or egg cells, the mutation can be transmitted to the person’s offspring. All mutations in the prion protein gene are inherited as dominant traits. Therefore, family history is helpful in considering the diagnosis. Several different mutations in the prion gene have been identified. The particular mutation found in each family affects how frequently the disease appears and what symptoms are most noticeable. However, not all people with mutations in the prion protein gene develop CJD. How is CJD transmitted? CJD cannot be transmitted through the air or through touching or most other forms of casual contact. Spouses and other household members of sporadic CJD patients have no higher risk of contracting the disease than the general population. However, exposure to brain tissue and spinal cord fluid from infected individuals should be avoided to prevent transmission of the disease through these materials. In some cases, CJD has spread to other people from grafts of dura mater (a tissue that covers the brain), transplanted corneas, implantation of inadequately sterilized electrodes in the brain, and injections of contaminated pituitary growth hormone derived from human pituitary glands taken from cadavers.

Doctors call these cases that are linked to medical procedures iatrogenic cases. Since 1985, all human growth hormone used in the United States has been synthesized by recombinant DNA procedures, which eliminates the risk of transmitting CJD by this route. The appearance of the new variant of CJD (nv-CJD or v-CJD) in several younger than average people in Great Britain and France has led to concern that BSE may be transmitted to humans through consumption of contaminated beef. Although laboratory tests have shown a strong similarity between the prions causing BSE and v-CJD, there is no direct proof to support this theory. Many people are concerned that it may be possible to transmit CJD through blood and related blood products such as plasma. Some animal studies suggest that contaminated blood and related products may transmit the disease, although this has never been shown in humans. If there are infectious agents in these fluids, they are probably in very low concentrations. Scientists do not know how many abnormal prions a person must receive before he or she develops CJD, so they do not know whether these fluids are potentially infectious or not.

They do know that, even though millions of people receive blood transfusions each year, there are no reported cases of someone contracting CJD from a transfusion. Even among people with hemophilia, who sometimes receive blood plasma concentrated from thousands of donors, there are no reported cases of CJD. While there is no evidence that blood from people with sporadic CJD is infectious, studies have found that infectious prions from BSE and vCJD may accumulate in the lymph nodes (which produce white blood cells), the spleen, and the tonsils. These findings suggest that blood transfusions from people with vCJD might transmit the disease. The possibility that blood from people with vCJD may be infectious has led to a policy preventing people in the United States from donating blood if they have resided for more than 3 months in a country or countries where BSE is common.` How can people avoid spreading the disease? To reduce the already very low risk of CJD transmission from one person to another, people should never donate blood, tissues, or organs if they have suspected or confirmed CJD, or if they are at increased risk because of a family history of the disease, a dura mater graft, or other factor.

Normal sterilization procedures such as cooking, washing, and boiling do not destroy prions. Caregivers, healthcare workers, and undertakers should take the following precautions when they are working with a person with CJD: Cover cuts and abrasions with waterproof dressings. Wear surgical gloves when handling a patient’s tissues and fluids or dressing the patient’s wounds. Avoid cutting or sticking themselves with instruments contaminated by the patient’s blood or other tissues. Use disposable bedclothes and other cloth for contact with the patient. If disposable materials are not available, regular cloth should be soaked in undiluted chlorine bleach for an hour or more, and then washed in a normal fashion after each use. Use face protection if there is a risk of splashing contaminated material such as blood or cerebrospinal fluid. Soak instruments that have come in contact with the patient in undiluted chlorine bleach for an hour or more, then use an autoclave (pressure cooker) to sterilize them in distilled water for at least one hour at 132 - 134 degrees Centigrade. Fact sheets listing additional precautions for healthcare workers and morticians are available from the NINDS and the World Health Organization. What research is taking place?

Many researchers are studying CJD. They are examining whether the transmissible agent is, in fact, a prion or a product of the infection, and are trying to discover factors that influence prion infectivity and how the disorder damages the brain. Using rodent models of the disease and brain tissue from autopsies, they are also trying to identify factors that influence susceptibility to the disease and that govern when in life the disease appears. They hope to use this knowledge to develop improved tests for CJD and to learn what changes ultimately kill the neurons so that effective treatments can be developed. How can I help research? Scientists are conducting biochemical analyses of brain tissue, blood, spinal fluid, urine, and serum in hope of determining the nature of the transmissible agent or agents causing Creutzfeldt-Jakob disease. To help with this research, they are seeking biopsy and autopsy tissue, blood, and cerebrospinal fluid from patients with CJD and related diseases. The following investigators have expressed an interest in receiving such material: Dr.

Pierluigi Gambetti, Director National Prion Disease Pathology Surveillance Center Institute of Pathology Room 419, Case Western Reserve University 2085 Adelbert Road Office of Communications and Public Liaison National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda, MD 20892 NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history. All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

Question: Christmas Disease is another name for one of the forms of which hereditary genetic disorder?
Answer: Haemophilia